This is a R21 application to test the hypothesis that effective new therapies can be developed for noninfectious inflammatory diseases of the cornea with either readily available adult stem/progenitor cells or the therapeutic proteins the cells produce in response to signals from injured tissues. The hypothesis will be tested through a collaboration between (a) the PI, a member of the National Academy of Sciences, who has been a pioneer in research with adult stem/progenitor cells known as MSCs, and (b) a fully-trained ophthalmologist and scientist (Joo Youn Oh, Co-Investigator). The hypothesis is based on the dramatic discovery by Dr.Oh that after a chemical burn to the cornea of a rat, application of MSCs or conditioned medium from MSCs reduced inflammation and neovascularization (Oh et al., 2008;Oh et al., 2009). Aim 1. Test the hypothesis that MSCs pre-activated in culture to express therapeutic proteins will be more effective in reducing inflammation and neovascularization following chemically-induced injury to the cornea than the standard cultures of MSCs used previously (Oh et al., 2008). Aim 2. Test the hypothesis that inflammation and neovascularization of the cornea can be reduced by application of two of the therapeutic proteins produced by activated MSCs: the anti- inflammatory protein TSG-6 and/or the anti-apoptotic protein STC-1. Aim 3. Use a previously successful strategy employed by the PI to search for additional therapeutic factors produced by MSCs in response to corneal injury. SIGNIFICANCE: If successful, the application will provide a basis for more effective therapies for the 750,000 Americans who each year suffer from acute and severe injuries of the cornea and for the 9 million Americans who suffer from dry eye syndrome. PUBLIC HEALTH RELEVANCE: There are no efficient and safe therapeutic strategies for corneal surface diseases ranging from quality-of-life deteriorating conditions (e.g. dry eye) to vision-threatening conditions (e.g. chemical burn). Most of these conditions are accompanied by noninfectious corneal inflammation and wound healing defects. This is a R21 application to test the hypothesis that effective new therapies can be developed for noninfectious inflammatory diseases of the cornea with either readily available adult stem/progenitor cells or the therapeutic proteins the cells produce in response to signals from injured tissues. If successful, the application will provide a basis for more effective therapies for the 750,000 Americans who each year suffer from acute and severe injuries of the cornea and for the 9 million Americans who suffer from dry eye syndrome.